Dr. Zamboni--the personal interview

December 11, 2011 at 9:41am

A wonderful interview with Dr. Zamboni in Il Giornale (the daily paper in Milano)

This piece answers many of our questions:  what disease does Dr. Zamboni have?  How is his wife doing?  How are the first group of patients doing?  What is going on with his CCSVI study?

Translated from Italian by google translate and me, a wonderful, indepth and personal interview.

Enjoy,

Joan

http://www.ilgiornale.it/interni/un_medico_malato_e_riuscito_curare_sclerosi_multipla/11-12-2011/articolo-id=561619-page=0-comments=1

By Stefano Lorinzetto-

A Medical Patient is able to treat Multiple Sclerosis

Progressing slowly in the hallway of Hospital Sant'Anna, walking on feet ballasted by orthopedic boots. He reaches towards me with both hands, unable to close them, but still able to transmit the warmth of empathy. Professor Paolo Zamboni, director of vascular diseases and professor of clinical methodology of the University of Ferrara, has a medical illness. He has been attacked - 'you do not know how, you do not know why '- by a very rare disease, probably from the immune system, which weakens the nerves and muscles. It's called MMN, multifocal motor neuropathy.  So far there are only a thousand cases between Europe and the United States. It is a mild form of ALS, amyotrophic lateral sclerosis.

But it's against another disease, MS, which Professor Zamboni has fought and won the hardest battle of his life. Wanting at all costs to heal his wife Elena, who had been hit, he did the logical thing for a scientist: "I tried to understand." The end point was the discovery of CCSVI, an acronym that made him famous in the world, so much so that now his surgery is booked until Easter, the switchboard of the study was replaced by a recorded voice that invites you to call at better times, the computer department of the hospital has accumulated 24,000 emails asking for medical examinations from those who can not cope, a Facebook group titled "Nobel Prize for Dr. Paolo Zamboni "has already gathered 7,957 supporters who would like to apply for the prize for medicine awarded by the Karolinska Institutet and Marco Marozzi has devoted a fascinating book of 334 pages, Brave Dreams (Knopf), which tells precisely" the struggle of a Italian doctor over multiple sclerosis."

CCSVI stands for chronic cerebrospinal venous insufficiency.  This is a major vascular disease that nobody before him had realized and that, as the Zamboni could ascertain, is present in 70 percent of patients with multiple sclerosis.  CCSVI is also found in 10 percent of people who do not have MS. It therefore remains to investigate everything from the role it plays in disease and other neurological degenerative diseases.

Professor Zamboni has overseen CCSVI surgery in collaboration with Dr. Fabrizio Salvi, MS expert and neurologist at Bellaria Hospital in Bologna. Dr. Salvi is so important to their research that when Salvi, big fan of motorcycles, ordered a Ducati Monster 900, the mechanics went to Zamboni and asked him: "Professor, but should we deliver it? And if he kills himself in an accident? With all the good that you have to do ...». The professor replied: "Right. Give him half capacity. "

The CCSVI procedure, under local anesthesia, takes 45 minutes to an hour and a half. It serves to unblock clogged veins. As part of a pilot study 65 MS patients were treated: 35 in the initial stage (the so-called relapsing-remitting form, with symptoms that come and go) and 30 had already needed to use a wheelchair. In 44 cases the operation is successful, the first time in 26 and 14 needed a second operation and 4 of a third. For 23 of the 35 patients in the first group was complete remission, only an MRI can detect the scars of MS.

Actually the most amazing results were achieved by Professor Zamboni on his wife, of whom he prefers, however, never to speak: "For ethical reasons I would not put her in the trial. So it's a case to be considered devoid of any scientific value. " So be it. The fact is that Elena feels good enough to make this point in the gym. This woman showed the first signs of the dreaded disease in December 1987, shortly after she gave birth to their daughter Matilda, who is now the fifth year of medical school.  Elena's procedure was done in May 2007 by Dr. Roberto Galeotti, the interventional radiologist who worked since 1998 with his childhood friend Paulo,  "Up until a moment before entering the operating room with Roberto, my mother-in-law went on to ask:" But are you sure of what you are doing? '" Since then Elena has had no more MS attacks. 

What is known about MS?

Not much, except that it is the most common degenerative disease in the age group 20-40 years. In the world you diagnose a case of MS every four hours. Those affected are 3 million, just over 61,000 in Italy."

When did he realize that his wife had MS? 

"We were just married. I had won a place as a researcher at the Institute of surgical pathology at the University of Sassari. Elena had followed me to Sardinia. One morning she phoned me: "It's as if I had ants on my face, I can not move the muscles of the face and I hear little from one ear." A few days later the strange noise ceased. There and then I gave it no importance. Five years later appeared the first episode, the one that occurs in half of MS patients: a black disc in the visual field. It is the immune system that attacks the optic nerve as if it were an enemy to destroy. The attack lasted for three weeks. Then another year and a half of peace. After which 'the precipice: she could not walk anymore, was not in balance. I felt inadequate as a husband and as a doctor, I was not able to answer her questions."

Reaction to the study. 

"Yes, I threw myself on the scientific literature of the treatment of MS. But I had trouble understanding. My colleagues see it as an autoimmune disease, an elegant formula by which we justify our ignorance as doctors. Juvenile diabetes, rheumatoid arthritis, nephritis, Crohn's disease ... We have to hurry, saying that all the wrong answers of the immune system. Including the MMN which I suffer. " 

And then? 

"I decided to start from scratch, studying pathological anatomy, from the microscope. And there I noticed something particularly interesting: at the center of each MS lesion passes a vein. Imagine a series: the vein is the thread, the plaques are the pearls. Without two decades of study I would never have come to discover the chronic cerebrospinal venous insufficiency. For the first time research on multiple sclerosis moved out of the skull, into the vessels of the neck and chest."

What does CCSVI do? 

"Three things. You can not achieve good oxygenation of brain tissue, and this can damage cells and nerves. CCSVI creates microbleeds and iron deposits in the veins of the brain, resulting in the production of free radicals. Increases inflammation and recall of immune cells. All three things considerably worsen the symptoms of MS. " 

Once taking care of CCSVI, what happens in people with multiple sclerosis? 

"MS has ten degrees of severity, ranging from normal to an apparent vegetative state. I can not say to those who are for years in a wheelchair, but surely removing CCSVI the symptom which disappears most, which is chronic fatigue, a fatigue so exhausting before that one cannot take on rehabilitation activities. Moreover, angioplasty strengthens the control of the sphincter. For a disabled person not to pee on himself may be more important than standing. He can return to the interest in life and social relations. " 

How is the operation? 

"Without a scalpel. It is an endovascular intervention. We introduce a thin catheter from the groin into the femoral vein and it sails under radiological guidance until the azygos, a vase-shaped walking stick vein, which is attached to the spine and behind the heart, which carries blood from from the spinal cord. The balloon catheter is inflated to remove the obstruction. The same is done on the two jugular veins. It is in these three locations that some thin membranes, possibly due to birth defects, impede the flow of blood. Unfortunately, in half the cases the membranes tend to reposition themselves after about eight months and must be done again. In 30 subjects out of 100 this second editing is final.

Why not remove the membrane once and for all? 

"It would need a special surgical instrument, but these are not being built because 'no manufacturer sets up an assembly line in the absence of a randomized trial." 

That is to say? 

"We need a double-blind tests, ie a clinical trial in which  'examiners ' and the patients do not know which of the latter were subjected to treatment. One is about to begin. It will be a study involving 700 patients--not for profit-- in fifteen Italian hospitals."

I know someone who has also beem nominated to participate is Nicoletta Mantovani, the widow of Luciano Pavarotti, She was diagnosed with MS in Los Angeles, six months after becoming the companion of the famous tenor. 

"She would have been entitled to the last place in the study that I conducted on 65 patients, but she did not want to give the impression of being special. She was the godmother of AISM, the Italian Multiple Sclerosis Association. And then she came out in protest against their attitude towards the closing of our research."

But Dr. Mark Freedman, director of the Multiple Sclerosis Research Unit, Ottawa Hospital, said: "I hear stories every day of complications from treatment abroad." And his colleague David Spence called robbery, robbery, to spend money and subject them to the care of the sick Zamboni: "It is the stuff of charlatans, quacks of medicine. No one is yet able to say if it works. " 

"If I had discovered something stupid, would they be opposed to this so much, do you think? Canada is the country in the world where MS is most striking, there is no family that does not have a relative or friend affected by multiple sclerosis. And Freedman is quoted as the neurologist in the fight against MS in Canada. I think I told you everything."

As stated in the book Bold Dreams, "there are those who live with multiple sclerosis and those living off of multiple sclerosis." 

"It is a disease modified with about 40 drugs manufactured by a dozen corporations, but in the last stages of the disease, the drugs are useless. A patient in Italy costs the NHS by 22,000 to 25,000 per year. An example: for the 500 MS treated with Vicenza Hospital San Bortolo will spend 11 million euros. Throw in the business connected with Disabilities: wheelchairs, prostheses, support aids, diapers."

And of his own disability, when he caught the first clue? 

"In the early nineties. After surgery I felt tired hands, heavy. Before that could operate for 12 hours straight without any problems. Then in 1994 a foot began to falter. For some years I used only the right hand. In 1998 I had to lay down the scalpel for good. Now I teach doctors who attend the school of specialization in general surgery. " 

What other activities, are not open to him? 

"The MMN leads to a progressive motor disability. Every gesture requires more patience, more fatigue. I learned to eat with your left hand and cut me from other steak in the dish. It takes me at least half an hour to dress, rather than 'two minutes. I can not best this tie. " (Laughs).

When I meet people like you, I always think back to a phrase. It is from a nineteenth-century painter, Ugo Bernasconi, "Better the doctor who heals us also makes us see his wound." 

"It's true. My patients, while seeing me sick, want to be sure that I am in the operating room too. Without hands, but with the head. I know that a more serious problem infuses much of their strength. " 

When did he explain to his daughter that her parents had been affected by serious diseases? 

"At age 15, she was with us at a medical conference in Poland. During the train trip I told her that mom and dad were suffering from diseases and what could be the outcome. In Warsaw, we had a night of forbidden things: cigarettes, beer and dancing on a table in a tavern. It was the last time I danced. " 

Gray matter atrophy in MS

December 8, 2011 at 1:05pm

For those who want more background on the importance of loss of gray matter in MS disease progression, here are some recent papers with explanation.

Gray matter atrophy means the loss of gray matter in the brain.  

It is a "wasting away" or death of the axons which make up brain tissue. This can be seen on MRI.  The death of gray matter is directly related to disease progression and disability levels in MS.

What's most important to understand is that gray matter atrophy happens independent of white matter lesions.  That's why Jeff has over 20 white matter lesions, but has had a reversal of gray matter atrophy since his CCSVI venoplasty almost 3 years ago.  His gray matter is plumper on his last MRI---it actually looks "normal."  And that gives us reason to celebrate.

People with MS should ask their neurologists "How does my gray matter look?"

If disease progression and disability are more closely linked to the rate of gray matter atrophy, it will give patients a better understanding of their own disease progression.

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From the Cleveland Clinic in 2008--a 4 year longitudinal study of gray matter atrophy.

To determine gray matter (GM) atrophy rates in multiple sclerosis (MS) patients at all stages of disease, and to identify predictors and clinical correlates of GM atrophy.

METHODS:

MS patients and healthy control subjects were observed over 4 years with standardized magnetic resonance imaging (MRI) and neurological examinations. Whole-brain, GM, and white matter atrophy rates were calculated. Subjects were categorized by disease status and disability progression to determine the clinical significance of atrophy. MRI predictors of atrophy were determined through multiple regression.

RESULTS:

Subjects included 17 healthy control subjects, 7 patients with clinically isolated syndromes, 36 patients with relapsing-remitting MS (RRMS), and 27 patients with secondary progressive MS (SPMS). Expressed as fold increase from control subjects, GM atrophy rate increased with disease stage, from 3.4-fold normal in clinically isolated syndromes patients converting to RRMS to 14-fold normal in SPMS. In contrast, white matter atrophy rates were constant across all MS disease stages at approximately 3-fold normal. GM atrophy correlated with disability. MRI measures of focal and diffuse tissue damage accounted for 62% of the variance in GM atrophy in RRMS, but there were no significant predictors of GM atrophy in SPMS.

INTERPRETATION:

Gray matter tissue damage dominates the pathological process as MS progresses, and underlies neurological disabillity. Imaging correlates of gray matter atrophy indicate that mechanisms differ in RRMS and SPMS. These findings demonstrate the clinical relevance of gray matter atrophy in MS, and underscore the need to understand its causes.

http://www.ncbi.nlm.nih.gov/pubmed/18661561

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Here's a study on gray matter loss in clinically isolated syndrome (CIS), or patients that have had one MS event, but are not officially diagnosed.  

How does the new gray matter research apply to CCSVI?

December 8, 2011 at 10:21am

If you haven't read yesterday's rather paradigm-shifting news about MS and the gray matter, look down a couple of posts.

In a nutshell--researchers from the Cleveland Clinic,  Mayo Clinic, and also Yale- have come forward with new evidence that confirms decades worth of research showing that MS is not primarily an autoimmune disease of the white matter, it is first a disease of gray matter.

The researchers admit that they do not know how current disease modifying drugs address cortical brain damage, and there are no current therapies created for this purpose.  This is most likely why MS disease progression continues while patients are on the drugs, even though relapse numbers may be diminished.  This is why gray matter atrophy is the biomarker for MS disease progression.

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 How does that fit in with Dr. Zamboni's discovery?  

The gray matter uses 94% of the brain's oxygen supply.  Because of this, gray matter is especially sensitive to any low oxygen environment.

The gray matter is densly packed with blood delivering capillaries.  The blood is what gives gray matter it's color and density.  Any endothelial dysfunction in this region can increase the risk of damage.  Any refluxive flow, break in the blood brain barrier, any iron or heme deposition into brain tissue from microvascular leakage, can affect this part of our brain and create inflammation.

In other words---adequate blood flow and perfusion is essential in this area of the brain.  For delivery of nutrients and oxygen, for removal of waste, for shear stress to maintain a healthy blood brain barrier.  Venous insufficiency and reflux is disasterous to the gray matter and can create inflammation.

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Many of the doctors involved in CCSVI research (Haacke, Hubbard, Dake) have written about the deep cerebral drainage of the cortex, and how this can be impacted by venous insufficiency.

New Research from Mayo, Cleveland and Yale--It's not about White Matter lesions, it's the Gray Matter

December 7, 2011 at 2:21pm

Readers of this page will know that we've discussed how white matter lesions are not really indicative of MS disease severity or progression.  That's why someone with over 20 white matter lesions, like my husband, can mountain bike, while a progressive patient with one lesion might not be able to walk.  It's not about the lesions. 

 But because this is what MRI technology could SEE, what EAE attempts to model, and what MS drugs could address---MS became a disease diagnosed and defined by white matter lesions. 

Gray matter atrophy and degredation,  noted in more refined MRI technology in research over the past decade, has provided a better biomarker of MS disease progression.  https://ccsviinms.blogspot.com/2016/01/thalamic-atrophy-and-ms-progression.html

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Before we get to the new research presented by the Mayo Clinic, Cleveland Clinic and Yale (spoiler alert--MS is not about white matter lesions)--let's get our terminology straight.

White matter--is called this because of the white-colored fatty protein covering of myelin that provides the insulation for axons.

White matter is found in the inner layer of the brain's cortex, the optic nerves, the brainstem and on the outside of the spinal cord.

Gray Matter-- is called this because it's actually grayish/pink-colored, since it carries the blood-rich capillaries.  Gray matter is found on the surface of the cerebral cortex and in the cerebellum, as well as in the depths of the cerebrllum....the thalamus, hypothalamus, basal ganglia, etc.   While the gray matter does have some myelinated axons, it does not have as much myelin as the white matter...thus, the difference in color.

Both of these studies looked at the outer layer of the cerebral CORTEX--which is gray matter.

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Now, on to the press release.....

I have bolded some of the words, because the researchers have "framed" this research to assert that immune modulating drugs are still the way to go.  We'll discuss after the press release.

http://www.bmedreport.com/archives/31937

From the Outside In: Mayo Clinic Collaboration Finds Multiple Sclerosis Often Starts in Brain’s Outer Layers

ROCHESTER, Minnesota -- Multiple sclerosis (MS) may progress from the outermost layers of the brain to its deep parts, and isn’t always an “inside-out” process as previously thought, reported a new collaborative study from researchers at the Mayo Clinic and the Cleveland Clinic. The traditional understanding is that the disease begins in the white matter that forms the bulk of the brain’s inside, and extends to involve the brain’s superficial layers, the cortex. Study findings support an opposite, outside-in process: from the cerebrospinal fluid-filled subarachnoid space, that cushions the outside of the brain and the cortex, into the white matter. The new findings will guide researchers as they seek to further understand and treat the disease. The study was published in the December issue of the New England Journal of Medicine.

Researchers do not know precisely what causes MS, but it is thought to be an autoimmune disease in which the body’s immune system attacks and destroys its own myelin. This fatty substance surrounds and protects axons, nerve cell projections that carry information, and its damage slows down or blocks messages between the brain and body, leading to MS symptoms, which can include blindness, numbness, paralysis, and thinking and memory problems.

“Our study shows the cortex is involved early in MS and may even be the initial target of disease,” says Claudia F. Lucchinetti, M.D., co-lead author of the study and Mayo Clinic neurologist. “Inflammation in the cortex must be considered when investigating the causes and progression of MS”, she says.

Study authors say current therapeutic options may not even address issues associated with the cortex. Understanding how the cortex is involved, therefore, is critical to creating new therapies for MS. “Measures of cortical damage will enhance enormously the power of clinical trials to determine if new medications address tissue changes of MS in all regions of the brain,” says co-lead author Richard Ransohoff, M.D., a Cleveland Clinic neurologist.

These measures are important because disease accumulates in the cortex over time, and inflammation in the cortex is a sign the disease has progressed.

The research is distinct because it studied brain tissues from patients in the earliest stages of MS. “What’s unique about the study is, and the reason the National MS Society funded this international team of researchers, is that it offers a rare view of MS early in the disease,” says Timothy Coetzee, Ph.D., Chief Research Officer at the National Multiple Sclerosis Society. “Collaborative studies like this, that deepen our understanding of the sequence of nervous system-damaging events, should offer new opportunities for stopping MS disease progression and improving quality of life for people with MS.”

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Here's a paper from Yale on the same topic--  Cortical Injury in MS--the role of the Immune System

http://www.biomedcentral.com/content/pdf/1471-2377-11-152.pdf

The Yale researchers call this an "emerging" picture of immune-associated cortical demyelination.  One might think they had coordinated the release of their paper at the same time as the Mayo Clinic and Cleveland Clinic.

Future work is necessary to more clearly define the emerging picture of immune-associated cortical demyelination that occurs in MS. Understanding the relationship between the profound inflammation commonly seen in the white matter and that of the cortex, which seems to be less consistently observed, is certainly a priority. Many other questions remain: From where do the meningeal infiltrates arise? Do the cells that populate these structures emerge from the periphery then migrate to this compartment or do pioneer naïve cells experience antigen in the CNS then proliferate exclusively within this compartment? How exactly do they affect tissue damage? Are these cells autoreactive? The antigen(s), whether they are self, environmental or unique to individuals, unquestionably need to be defined. While important recent findings have strengthened our understanding of MS cortical tissue damage they also highlight the critical need to further understand cortical pathology and pathogenesis 

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So.  Although the researchers don't mention these points in the cheery press release, it might be good to state:

1. White matter lesions are not MS.  

2. The classic EAE model is not MS, since the effect of EAE on the cortex is not well known.

3. We do not know for sure how current disease modulating drugs, created to ameliorate EAE,  will affect the cortex, or even if they have any impact on disease progression at all.

4. Although the science is not in yet, it is "overwhelmingly likely" that this cortical damage is due to the immune system.  Really?   Researchers can "weave together" their theory using animal models?  Really?

5. How do we account for the high levels of iron deposition in deep gray matter as noted on SWI technology?  Venous reflux and stasis, anyone?   Iron deposition would most certainly create inflammation in the brain.  Perhaps the researchers might want to look at Dr. Haacke and Dr. Zivadinov's research before deciding that it's just aberrant inflammation.

http://www.ajnr.org/content/early/2011/11/24/ajnr.A2773.abstract

6. Ischemic injury and reperfusion is known to create inflammation in the cortex.

http://www.nature.com/jcbfm/journal/v24/n12/full/9591642a.html

7. Cortical demyelination and inflammation is noted in dementia in the elderly, and stroke

http://stroke.ahajournals.org/content/35/2/410.full.pdf

8.  And finally, and importantly, I found many other studies asserting that cortical demyelination in MS is not immune modulated.

http://www.mendeley.com/research/meningeal-inflammation-is-not-associated-with-cortical-demyelination-in-chronic-multiple-sclerosis/

http://brain.oxfordjournals.org/content/128/11/2705.full

http://www.nature.com/nrneurol/journal/v6/n8/full/nrneurol.2010.93.html

http://www.ingentaconnect.com/content/mksg/ane/2001/00000103/00000005/art00024

I am consistently amazed at how MS specialists and researchers are able to make the "reassuring" leap that MS is immune modulated, even when everything they thought they knew about the disease turns out to be wrong.

Joan

How Hypoxia creates Inflammation--New England Journal of Medicine

November 29, 2011 at 9:44am

Found a great paper in the New England Journal of Medicine that discusses how hypoxic environments, like high altitudes, can create inflammation and signal the immune system in the brain.  It was written by some specialists in high altitude and hypoxia, researchers at the University of Colorado in Denver.

In persons with mountain sickness, for example, levels of circulating proinflammatory cytokines increase, and leakage of fluid ("vascular leakage") causes pulmonary or cerebral edema.  Increased serum levels of interleukin-6, the interleukin-6 receptor, and c-reactive protein--all markers of inflammation--were increased in healthy volunteers who spent 3 nights at an elevation higher than 3400 m.  The development of inflammation in response to hypoxia is clinically relevant.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930928/

All it took to create higher levels of serum inflammation in healthy people was 3 nights.

My husband Jeff came home from the Sundance Film Festival in Salt Lake City in his first, soon to be diagnosed MS flare.  His serum inflammation numbers were through the roof.  And that's how this journey began for us.   

Slowed perfusion and collateral circulation created by truncular venous malformations can create a low oxygen environment in the brain and start the inflammatory process.  Understanding the link to the high levels of MS diagnosis in new residents to Colorado would be a great place to start.

Joan

Venous intraluminal abnormalities in MS

October 30, 2011 at 12:02pm

A medical student from Case Western University has been providing some interesting research in the US for CCSVI.

Claudiu Diaconu first presented his research proposal to study CCSVI in November 2010 at the Lepow Day at Case Western.  This is a yearly event, where medical students present their research projects.  Diaconu's was called:  An Assessment of Chronic Cerebrospinal Venous Insufficiency -Tissue Analysis of the Cerebrospinal Veins.  His study was funded with a grant from the NMSS.

In his proposal, Diaconu set out how he would harvest the autopsied veins and inject them with a silicone gel in the lab, so that the interior of the vein could be studied.  This was one part of his study, which also included doppler ultrasound and MRV assessment of CCSVI.

At ECTRIMS, Claudiu Diaconu's research created a bit of a stir.  A year after his proposal he came forward with evidence of the truncular venous malformations associated with CCSVI.  The intraluminal defects that Dr. Zamboni has been describing for years.

The same Cleveland Clinic group also has begun examining cerebrospinal veins from cadavers of MS patients and controls.

Some results from the first 13 cadavers were presented during a platform session at ECTRIMS by Case Western University medical student Claudiu Diaconu. He confirmed that venous structures in the brain and brainstem appear to be far more complicated and variable than previously thought.

In fact, the postmortem study revealed the presence of a novel venous valve that had not been described in anatomy textbooks.

Perhaps the most important finding was that most of the stenoses identified in the study were not associated with vessel wall thickness or circumference.

As a result, Diaconu said, cerebrospinal vein scans in live patients "should focus on identifying intraluminal abnormalities, not just vessel wall narrowing or thickening.

link

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And the results of his study, so far, are found in this abstract-

link

Anatomical and histological analysis of venous structures associated with chronic cerebrospinal venous insufficiency

Marked valvular and other intraluminal abnormalities with potential hemodynamic consequences were identified in 5 of 7 MS patients (7 abnormalities) and in 1 of 6 controls (1 abnormality). These abnormalities included circumferential membranous structures (1 MS and 1 control), longitudinally-oriented membranous structures (3 MS), single valve flap replacing IJV valve (2 MS), and enlarged and malpositioned valve leaflets (1 MS). In addition, minor anatomic variations without expected hemodynamic consequences were observed similarly in both MS and controls. These included valves with >2 leaflets, the presence of valves in the AZY, additional (duplicate) normal-appearing IJV valves, and small membranous septa. 

Conclusion: Post mortem examination of the IJV and AZY veins of MS patients and non-MS controls demonstrated a variety of structural abnormalities and anatomic variations. Vein wall stenosis occurred at similar frequency in MS and non-MS controls. However, the frequency of intraluminal abnormalities with possible hemodynamic consequences was higher in MS patients compared to healthy controls, although the current sample size is limited.

It is this type of inquisitive and open collaboration of medical practices which will elucidate the connection of CCSVI and MS, and help us move forward, as doctors understand the best means to deal with these intraluminal defects.  

These are mechanical defects, which means there is no money for pharmaceutical companies, and less money for research.  But there are answers to be found, and help and healing for those with MS.   

Joan

At the Cleveland Clinic, technician Larry Raber and physician Mei Lu practice the ultrasound technique to measure CCSVI in patients with MS on medical student Claudiu Diaconu. Cleveland Clinic Center for Medical Art

Shift Work, Cortisol and Environmental Factors in MS

October 19, 2011 at 8:11am

In the news yesterday, a new study showing how shift work (night time work outside of normal daytime hours) doubles a teen's risk of developing Multiple Sclerosis.  

This is considered an "environmental factor" as opposed to a genetic factor.  This new paper comes from the Karolinska Institute in Sweden and was published in the Annals of Neurology.  The researchers did not propose a specific theory as to how shift work might increase the risk of MS, but they did comment on how circadian rhythm disruption might affect melatonin and the immune system.

Here is the complete paper:

http://sverigesradio.se/diverse/appdata/isidor/files/83/11395.pdf

Oddly enough, just last week, another published study showed how shift work raises the risk of metabolic disease, higher body mass index (BMI) and cardiac problems in young adults vias cortisol release. This study was undertaken by Dutch researchers and published in the Journal of Clinical Endocrinology-- only a week prior to the Swedish study.  

Here's the abstract for that paper on shift work:

http://jcem.endojournals.org/content/early/2011/08/25/jc.2011-1551.abstract

Shift work, or work outside standard daytime hours, has been associated with an increased incidence of metabolic syndrome, and cortisol plays a major role in the development of the disease.

Glutathione and loving your liver

September 25, 2011 at 2:02pm

Dr. David Perlmutter has pioneered glutathione treatment and believes it can be helpful in neurological diseases, including MS and Parkinson's Disease.  And it has helped many.

Glutathione is a super antioxidant, but taken orally, it doesn't really do well.  The digestive tract breaks it down before it can become available in the rest of the body.  It's great as an IV infusion,  but this isn't readily available to many.  So, I thought I would explain a bit about glutathione, and how we can increase the production in our own bodies.  The truth is, the best way to increase glutathione is not to ingest it or use an IV, it's to let your body make it itself.

Glutathione is naturally created by a healthy liver.  

When Jeff was diagnosed with MS, one of his strange blood results was that his liver enzymes, AST and ALT, were 10 times higher than normal. He was slightly jaundiced and his eyes were a bit yellow.   It looked like he had liver disease, and his neurologist assumed he drank too much alcohol, but Jeff didn't drink.  So I did some research, and learned that high liver enzymes happened in those w/MS---even before taking any drugs.

Multiple Sclerosis Linked to Abnormal Liver Test Results- 

To make the link, the researchers used data from the Sylvia Lawry Centre for MS Research in Germany, the largest database of MS clinical trial information in the world. In all, medical information from 813 people with MS enrolled in various clinical trials from North America, Australia and Europe was analyzed. The study was funded by the MS Society of Canada. 

Over a two-year period, there was an over three-fold increased risk of a person with MS having an elevated liver test result compared to expectations. An elevated test result indicates that liver enzymes have leaked out of their cells. This leakage into the blood stream may be an indicator of liver cell damage. 

http://www.mssociety.ca/en/releases/nr_20061101.htm 

Dr. Dake on "retinal vein sheathing": MS-like lesions, but no myelin

September 16, 2011 at 7:57pm

Dr. Dake made a very important point for the CIRSE conference with his in depth essay on the importance of CCSVI research. 

Retinal Vein Sheathing in MS--  The veins of the retina in pwMS become enlarged and thickened and there is damage to the retinal nerves.  Without myelin.  99% of the time, there is no myelin on retinal nerves, but there is MS damage.  

Here's Dr. Dake---

Underappreciated in the midst of these clashing positions is one other example of a similar venous lesion with potential relevance to MS – sheathing of retinal veins. This cuffing or sheathing of veins can be appreciated on fundoscopic examination of the eyes and may be associated with retinal vein thrombosis, optic neuritis and vision loss. 

In the majority of cases when it is diagnosed during an evaluation of disturbed vision, it occurs in patients with MS. Studied extensively at the Mayo Clinic, it is not however singularly associated with cases of established MS. Its frequency among MS patients is estimated to range from 11% to 42%. After fluoroscein dye administration, it is possible to observe leakage of dye around the retinal veins and histologically, the veins display a thickened wall similar to appearances observed in other chronically obstructed venous territories.

When contemplating the possible association between venous obstruction, blood-brain barrier leakage, myelin destruction and immune mechanisms responsible for the initiation of MS, it is interesting to note that the retinal nerve fibres are not myelinated in 99% of the population.

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Lesions due to MS, occuring on nerves that do not have myelin.  Leaking veins--in people who develop MS.  "Cuffs" that contain immune cells around these leaking veins.

The optic nerve, which exits the back of the eyeball, DOES have myelin.  The retinal nerve sheath, inside the eyeball, does not.

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These vascular abnormalities of the eyes in pwMS have been noted by opthamologists for decades.

Here's a paper from 1986

New, Independent research from Serbia

September 12, 2011 at 9:10am

A new paper was recently published in Phlebology, Sept. 2011 issue.

Morphological and haemodynamic abnormalities in the jugular veins of patients with multiple sclerosis

D Radak, J Kolar, S Tanaskovic, D Sagic, Z Antonic, A Mitrasinovic, S Babic, D Nenezic and N Ilijevski Vascular Surgery Clinic, Dedinje Cardiovascular Institute, School of Medicine, Belgrade University, Heroja Milana Tepic ́a 1 Street, Belgrade, Serbia

(This study was not conducted by neurologists, nor was it funded with pharmaceutical monies.  These are vascular doctors --This study was partly funded by the Serbian Ministry of Science and Techonological Development – Project No. 41002.)

I have the full paper, and will break down what the researchers discovered.  

First, it is important to note that they only looked at the jugular veins with doppler.  No transcranial doppler, per the Zamboni criteria, and no venography or azygous.  These researchers wanted to see if they could find "morphological and haemodynamic abnormalities" in the jugular veins.  This means they were looking for physical irregularities and flow distubances in pwMS.  Not completely CCSVI, per Dr. Zamboni's definition.

The limitation of our study is that we did not examine the CCSVI prevalence in patients with MS because we did not investigate the intracranial and vertebral veins. The aim of our study was to evaluate morphological and haemodynamic IJV abnormalities in patients with MS and compare it with healthy controls. For morphological and haemodynamic abnormalities assessment of the IJVs, we used some of Zamboni’s criteria and two other parameters (parameters 1 and 2), which in our practice proved to be a good indicator of IJV flow disorder.

--What they were surprised to discover was that the IJV flow was very different in pwMS, and that they could pick this up with doppler ultrasound.

All these might result in IJV haemodynamics changes that could be assessed by non-invasive and cost-effective colour duplex sonography.6 The main finding of this study was to demonstrate a significantly higher prevalence of morphological and Doppler haemodynamics abnormalities in patients with MS in relation to healthy subjects.

Our study showed that 42% of the patients with MS had Doppler haemodynamic evidence of venous flow abnormalities as compared with 8.1% of the healthy controls. These data not only indicate that venous flow abnormalities were significantly associated with the presence of MS but also indicate that it can be seen in the population not suffering from MS, yet the difference remains statistically significant (P , 0.001).

--Also interesting was that they found faulty valves and stenosing lesions in some of the normal controls, but these irregularities didn't affect the blood flow as much as they did in pwMS.

Blocked blood vessels:  New research from Rush University

September 1, 2011 at 1:28pm

Dr. Aron Buchman is a neurologist at Rush University in Chicago.  For the past 20 years, he has been studying the aging brain and subtle changes that preceed Alzheimer's and Parkinson's diagnoses.  Here is the press regarding his most recent study, which looks at the brains after the participants have passed---

http://www.eurekalert.org/pub_releases/2011-09/rumc-soa082911.php

Signs of aging may be linked to undetected blocked brain blood vessels

Many common signs of aging, such as shaking hands, stooped posture and walking slower, may be due to tiny blocked vessels in the brain that can't be detected by current technology.

In a study reported in Stroke: Journal of the American Heart Association, researchers from Rush University Medical Center, Chicago, examined brain autopsies of older people and found:

Microscopic lesions or infarcts — too small to be detected using brain imaging — were in 30 percent of the brains of people who had no diagnosed brain disease or stroke.

Those who had the most trouble walking had multiple brain lesions. Two-thirds of the people had at least one blood vessel abnormality, suggesting a possible link between the blocked vessels and the familiar signs of aging.

"This is very surprising," said Dr. Aron S. Buchman, lead author of the study and associate professor of neurological sciences at Rush. "The public health implications are significant because we are not identifying the 30 percent who have undiagnosed small vessel disease that is not picked up by current technology. We need additional tools in order to identify this population."

The Chinese and MS

August 27, 2011 at 2:45pm

Looking at the Chinese as a population has been very useful when studying chronic diseases.

According to Multiple Sclerosis International, the prevalence of MS in China is between one and 50 for every 100,000 people. The situation, however, changes when looking at immigrants who have come to Canada from countries where the exposure to the sun is different.

Canadians of Chinese origin were 10 times more likely to have MS than people in China, Savoie said. "Some of them have more severe MS than Canadian counterparts of Caucasian origin and that may tell us something about the fact that when you move across the globe, you're reacting, in fact, to these changes in the environment, including changes in exposure to vitamin D."

http://news.xinhuanet.com/english2010/health/2011-08/26/c_131077336.htm 

Vitamin D is obviously a very important component in this discussion, as most of Canada is at a northern latitude compared to China.  But the Chinese are also have problems with vitamin D deficiencies in their own country.

Subclinical vitamin D deficiency was widespread among Beijing adolescent girls in winter. Low plasma 25-hydroxyvitamin D concentrations in summer, low calcium intake, and low plasma calcium concentrations in winter were the main risk factors for vitamin D deficiency in winter.

http://www.ajcn.org/content/74/4/494.short

What else changes for Chinese people who move to Canada?  What other factors are new to them?

The western diet.  

This has been studied in relationship to the endothelium and heart disease by Dr. T. Colin Campbell.

BNAC review: Venous stasis and EBV, viruses and bacteria

August 24, 2011 at 9:19pm

It is quite possible that venous stasis, or slowed cerebral drainage, could be responsible for the number of viruses (such as EBV and HHV) and bacteria (such as Cpn and Lyme) that have been associated with MS-by allowing these infectious agents to pass through the blood brain barrier.  Here is the Buffalo review on this topic:

The association between EBV infection and CCSVI has not yet been explored; however, it could be hypothesized that venous stasis in the superior saggital sinus due to extracranial outflow impairment could affect the drainage of bridging veins that pass through the subarachnoid space (near the meninges and EBV-infected B-cell follicles) and contribute to EBV activation. The venous stasis hypothesis in the SSS may contribute to understanding why so many different viruses and bacteria [3,111] have been linked to increased MS susceptibility risk over the last 50 years.

http://www.expert-reviews.com/doi/abs/10.1586/ern.11.117

The blood brain barrier is supposed to keep viruses and bacteria out of the central nervous system.  Venous stasis, or slowed blood flow, would explain why so many infectious cells are passing into the brain and spine in MS.  It just makes sense!   More studies ahead.

Joan

 Dr. Zamboni-his frustration with the neurological journals using opinion pieces, not science

August 12, 2011 at 3:22pm

In a recent article in MedScape discussing the OPINION of Dr. Compston that new genes found in MS implicate the immune system only, and preclude a vascular connection,  Medscape asks Dr. Zamboni for his opinion on this new research and the recently published negative review by Dr. Bagert (both negative pieces were all over the corporate owned press.)

Asked to comment on the review by Dr. Bagert and colleagues, Dr. Zamboni expressed some exasperation that the review again does not represent actual new evidence, but is a review, including opinion pieces.

"Until a few years ago, the Archives of Neurology had a section of great interest [called] Controversies, where the reader had the opportunity to consider different visions," said Dr. Zamboni, who is director of the Vascular Diseases Center at the University of Ferrara, Italy.

"Nowadays, countless editorials and opinion articles about CCSVI have been invited in journals of clinical neurology with no chance to reply. This habit, certainly not academic, helps to make me a defendant in science, just to get reported in 30 peer-review articles an underdeveloped aspect of MS research," he told Medscape Medical News.

In their review article, Dr. Bagert and colleagues refer to the Bradford Hill Criteria that are used to assess scientific evidence of causation in biological systems and suggest that in this case, "there is very little validated scientific evidence to support the theory that CCSVI is the cause of MS, especially among the criteria of biological plausibility, coherence, and analogy."

To this point, Dr. Zamboni responds that he would like to see the authors apply the Bradford Hill Criteria, citing exclusively original articles and not editorials and opinions. If his own work is scientifically inaccurate by these criteria, then so is much of the epidemiologic data in other aspects of MS, he says, where studies are equally inconsistent in sample sizes and methods of data collection.

Of the studies published to date on CCSVI, despite the high variability, MS is associated with CCSVI in an average of 80% of cases vs 10% of the healthy population, Dr. Zamboni asserts.

"Furthermore, with respect to the biological plausibility and the coherence of Bradford Hill Criteria, the autoimmune theory cannot in turn explain several vascular aspects well detailed in the MS literature," he toldMedscape Medical News.